TRIM3通过调控PIAS1-STAT1轴抑制胶质瘤发生发展

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【中图分类号】 R739.41 【文献标志码】 A 【文章编号】1672-7770（2025）02-0149-10

Abstract： Objective To explore the role and molecular mechanisms TRIM3 in the occurrence and development human glioblastoma through PIAS1-STAT1. Methods Lentiviral overexpression TRIM3 and shRNA-transfected GBM cell lines U251 and U87 were constructed， with corresponding control groups CON335 and CON313. The FLAG-TRIM3 plasmid was used to transfect GBM cells and 293T cells， to construct overexpression cell lines. Living cell counting （CCK-8）， plate cloning experiments， Transwell chambers， and flow cytometry were used to analyze the proliferative activity， clumping， migration ability， and apoptosis glioma cells. Western blot and co-immunoprecipitation（Co-IP） experiments were conducted to detect the interaction between TRIM3 and PIAS1 proteins， as well as the specific molecular mechanisms. Real-time quantitative fluorescent polymerase chain reaction（ PCR） was used to detect the mRNA expression TRIM3 and PIASI. Dual-luciferase reporter gene assays were employed to test the impact TRIM3 on STAT1 activity. Nude mouse intracranial tumor models were used to demonstrate the impact TRIM3 on glioma formation in vivo. Results Compared to normal brain tissue cells， the expression TRIM3 was significantly reduced in GBM tissues. The expression level TRIM3 decreased with the WHO grades. Overexpression TRIM3 in glioma cells resulted in a significant attenuation their proliferative， clumping，and migratory capacities， and induced apoptosis in GBM cells. Western blot analysis revealed that overexpression TRIM3 in GBM cells was associated with a concentrationdependent reduction in PIASl protein levels. Real-time quantitative PCR data indicated that TRIM3 overexpression had no influence on the mRNA levels PIASl and STATl. Dual-luciferase reporter assays confirmed that TRIM3 enhances the transcriptional activity STATl. Moreover， TRIM3 mediated the degradation PIAS1 by promoting its poly-ubiquitination at the K48 residue， thus alleviating the suppressive effect PIAS1 on STATl transcription. In vivo studies using a nude mouse model demonstrated that， relative to the control group， the rate and size intracranial tumor formation were significantly reduced in mice with overexpressed TRIM3. ConclusionsTRIM3 disrupts the PIAS1-TRIM3 axis， suppressing glioma progression， and fers a novel therapeutic target.

Key words： gliobastoma； TRIM3 ； PIAS1 ； STAT1 ； ubiquitination

胶质母细胞瘤（glioblastoma，GBM）作为成人中枢神经系统中最常见的原发性恶性肿瘤，恶性程度极高。（剩余16111字）